Girls at high risk for depression but without current or past clinically significant symptoms showed abnormal brain function related to anticipating and receiving either a reward or loss, according to a study funded by the National Institute of Mental Health (NIMH). According to the researchers, this abnormal brain function may be useful for predicting future illness in people with a family history of depression. The study was published in the April 2010 issue of the Archives of General Psychiatry.

Background

Past research has shown that depression is associated with faulty processing in certain brain regions, but it is unclear whether abnormal functioning precedes depression or is caused by it.

For their study, Ian Gotlib, Ph.D., of Stanford University, and colleagues compared 13 girls whose biological mothers had a history of recurrent episodes of major depression (high-risk group) with 13 girls who had no family history of depression (low-risk group). All of the girls were between the ages of 10 and 14, and none had either past or current major depression.

Using functional magnetic resonance imaging (fMRI), the researchers assessed the participants' brain function during a series of tasks that involved responding quickly to different cues to win points or avoid losing points that could later be exchanged for prizes. Each task was preceded by a cue signaling the type of task that would follow (win points or avoid losing points). During this phase, the researchers observed brain activity related to anticipating reward or loss. After each task, participants received feedback about the number of points they had gained or lost according to how they performed. During this phase, the researchers studied how the girls' brains processed the experience of reward or loss.

Results of the Study

When compared to girls in the low-risk group, girls at high risk for depression showed abnormal brain functioning related to anticipating and processing reward and loss. Specifically, they showed:

Reduced brain activation during reward processing

Greater activity while anticipating reward in a brain area linked to anticipating aversive events, such as a scary image or a painful shock

Greater activity following losses in an area associated with learning from experience, but no activity in reward processing; in contrast, low-risk girls activated this area during reward processing but not loss outcomes.

Significance

According to the researchers, their study suggests that familial risk for depression affects brain activity and function before the onset of depressive symptoms. These findings complement another recent finding from these investigators that girls at high risk for depression have smaller hippocampi—a brain structure involved in regulating stress and emotions—than do girls with no family history of the disorder.1

What's Next

Abnormal reward and loss processing in the structures identified in this study may serve as useful biomarkers of depression risk. However, further research is needed to determine how affected brain processes may change over time and whether they can be used to predict the onset of depression.